Sleep Position May Boost Epilepsy Death Risk

by John Gever John Gever Managing Editor, MedPage Today
January 21, 2015

Action Points

Note that this meta-analysis of case reports of sudden unexpected death in epilepsy found that a significant number of patients were found to be prone after death.

Be aware that, without data regarding the prevalence of prone-sleeping in the at-risk population, no formal association between prone sleeping and SUDEP can be assessed.

People with epilepsy who sleep on their stomachs may be at increased risk for sudden death, a review of more than 250 cases suggested.

Among 253 instances of sudden unexplained death in epilepsy (SUDEP) in which body position was documented, nearly three-quarters of the victims -- 73.3% (95% CI 65.7%-80.9%) -- were found in a prone position, according to James X. Tao, MD, PhD, of the University of Chicago, and colleagues.

"In addition, the prone position was reported in all 11 cases of video-EEG-monitored SUDEP," the researchers noted in their report, published online in Neurology.

They also found that the association was somewhat stronger in SUDEP patients 40 and younger, among whom the prone-position rate was about 86%, versus 60% in those older than 40 (odds ratio 3.9, 95% CI 1.4-11.4, P=0.009).

Tao and colleagues stopped short of making a similar recommendation for epilepsy patients, citing the limitations of their study and noting other potential contributors to SUDEP risk. Instead, they called for additional research and documentation of sleep position in future SUDEP cases whenever possible.

These cautions were echoed in an accompanying editorial by Barbara Dworetzky, MD, of Brigham and Women's Hospital in Boston, and Stephan Schuele, MD, MPH, of Northwestern University's Feinberg School of Medicine in Chicago.

Because of the retrospective design, the analysis "cannot answer whether sleeping in a prone position is more prevalent among patients with epilepsy who die of SUDEP, or how many patients change body position during or after the terminal seizure," they wrote.

Nevertheless, they indicated, "[d]iscovering a possible modifiable risk factor for SUDEP, such as sleeping in the prone position, is clearly important because it implies the possibility of preventing a substantial number of deaths by having patients sleep on their back, as has been done with SIDS."

Dworetzky and Schuele added, "the study underlines that simple measures may have a substantial effect on SUDEP risk and that our efforts to attend to patients and bring them out of a prone position are worthwhile."

Study Details

For their analysis, Tao and colleagues drew on case series and individual case reports published in the medical literature, identified from searches of online indexes such as PubMed. Cases were considered SUDEP when status epilepticus or an identifiable cause of death were clearly not present. The researchers reviewed more than 1,100 such reports, of which 25 had no overlap in patients and included information on body position (prone, supine, sitting, or lateral). These reports covered a total of 253 patients.

Of these 253, 183 were found in a prone position. For about half the others, the reports only indicated that they were not found prone. Twenty-seven were reported as supine, five as sitting, and one as lateral.

The study also revealed some details of the 11 SUDEP cases occurring while patients were undergoing video-EEG monitoring. Although the video recordings showed victims in a prone position at some point in all cases, only four were sleeping prone prior to onset of the terminal seizure. Three rolled into a prone position during seizures, Tao and colleagues indicated.

Circadian data were available for 84 of the cases. Of these, 63 occurred during sleep and 21 while patients were awake. Even in this latter group, 13 (62%) were found in a prone position at death.

Prone positioning was about equally common in male versus female SUDEP cases.

Unfortunately, Tao and colleagues noted, their study shed little light on one of the central mysteries of SUDEP -- the exact mechanism of death. Real-time oxygen and carbon dioxide monitoring was not performed during any of the episodes included in the analysis, which might have indicated whether suffocation was a factor.

In all of the 11 cases with video-EEG monitoring, victims had undergone generalized tonic-clonic seizures with postictal generalized EEG suppression. But this observation, by itself, was not especially novel, as a history of such seizures is already a well-known risk factor for SUDEP.

But Tao and colleagues argued that the conjunction of such seizures with prone positioning in all 11 cases was an important finding: "These commonalities cannot be simply a matter of chance. Instead, they likely reflect a common mechanism," the researchers wrote.

They also suggested that the parallels with SIDS may suggest a mechanism for SUDEP, with serotonergic pathways as a mediator.

"Serotonergic neurons in the brainstem regulate both respiration and arousal in response to the fluctuation of blood CO2 and maintain pH homeostasis," they wrote. "In SIDS patients, impaired arousal secondary to serotonin deficiency can suppress autoresuscitation mechanisms and prevent them from lifting or turning their heads when their airway is obstructed by soft bedding in a prone position."

Combining these observations with the overwhelming prevalence of prone positioning in the current study, Tao and colleagues proposed a model in which body position is one of three components of a fatal cascade, the other being the presence of generalized tonic-clonic seizures and postictal EEG suppression.

"Convergence of these three in a patient is likely to have a major role in many patients who experience SUDEP," they hypothesized.

Limitations to the analysis, they acknowledged, included the reliance on literature searches and previously published reports for their data, which are subject to multiple potential biases. Also, body position prior to seizure onset was not known in most of the cases, and there was no data on possible airway obstruction or other respiratory or cardiac parameters that may have suggested actual causes of death.

The study had no dedicated funding. Tao and colleagues declared they had no relevant financial interests.

The editorialists reported relationships with SleepMed, Sunovion, GlaxoSmithKline, and Supernus.

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